The long-term objective of our research is to elucidate mechanisms which regulate gene expression in both normal and neoplastic tissues. We will employ normal liver, liver during hepatocarcinogenesis, various hepatomas, cellular and nuclear suspensions prepared therefrom and will: (a) Determine whether pretranslational control is general in tumors. We will extend our recent studies which demonstrated that deletion of tryptophan oxygenase and a 2u globulin from hepatomas was due to the absence of their corresponding specific mRNA species; we will determine whether synthesis of tumor specific (carcinofetal) proteins as well as new isozymic species, e.g., pyruvate kinase and LDH, are also consequences of altered specific mRNA levels. (b) Employ our recently developed procedures and isolate the specific mRNAs of a 2u globulin and tryptophan oxygenase. We will prepare their radioactive cDNAs and determine gene dosage, ratio of nuclear to cytoplasmic levels of specific mRNA species, and employing mercurated nucleotides in conjunction with these specific mRNA sequences in liver, in hepatomas, during hepatocarcinogenesis and during endocrine control. (c) Study the nature of the nuclear sites interacting with glucocorticoid-receptor complex and its relationship with hepatocarcinogens. (d) Continue our attempts to characterize the nuclear events by which steroid-receptor complex regulates gene transcription and/or processing of the gene transcript into functional mRNA for the hormonally inducible enzymes. (e) Employ cell hybrids to attempt to determine whether gene products are positive or negative modulators controlling the expression of eukaryotic processes by which several hormones coordinate to regulate the rate of synthesis of the proteins a2u globulin and tyrosine aminotransferase.